Despite the presence of famous cultivations of lemons (the meaning of limone in Italian), the town's name is probably derived from the ancient lemos (elm) or limes (Latin: boundary, referring to the communes of Brescia and the Bishopric of Trento).

On 13 September 1786, the famous German poet J. Wolfgang Goethe passed by the village by boat and described with these words its lemon gardens: (Italian Journey, J. Wolfgang Goethe, 1816–17)[4] Until the 1940s, the town was reachable only by lake or through the mountains, with the road to Riva del Garda being completed in 1932, but today Limone is one of the most renowned tourist resorts in the area.

[5] The protein appears to have given residents of the village extreme longevity - a dozen of those living here are over the age of 100 (for c. 1,000 total inhabitants).

[citation needed] The origin of the mutation has been traced back to a couple who lived in Limone in the 17th century.

[6] Research has been ongoing to develop pharmaceutical treatments against heart disease based on mimicking the beneficial effects of the ApoA-1 mutation.